PROJECT SUMMARY Nicotine use is typically initiated in adolescence?more than 90% of smokers begin smoking before the age of 18?yet not enough is known regarding how nicotine may affect adolescent brain development into adulthood. During adolescence, the dopaminergic system and dopamine D2 receptor (D2R) levels in particular are in flux. The effects of nicotine exposure during this developmentally crucial time may lead to changes in D2R levels that persist into adulthood. Since an individual's D2R levels are thought to affect cognition, mood, and addictive as well as other problem behaviors, it is of the utmost importance to investigate whether nicotine exposure in adolescence can enact long-lasting alterations to D2R binding in the adult brain. Ethical limitations mandate that this question cannot be directly studied in adolescent humans, and thus information can only be derived from animal models. This project combines PET imaging with a rat model of adolescent nicotine use, allowing for the in-vivo characterization of the effects of early nicotine exposure on adult dopamine receptor levels. This research has three specific aims, to: 1. Characterize in-vivo baseline D2R binding in the adolescent brain (P30) compared to the adult brain (P60). 2. Determine the effect of chronic adolescent (P30) nicotine exposure on D2R binding in-vivo in adult rats (P60). 3. Determine the effect of adult-onset (P60) chronic nicotine exposure on D2R binding in-vivo in adult rats (P90). PET imaging will be performed using [11C]raclopride to measure D2R binding. We will first image rats at baseline in early adolescence or early adulthood. We will then treat each age group with twice daily doses of nicotine for two weeks, followed by a 16-day period of cessation. On the last day of cessation, we will conduct the post-treatment scan. We will follow the same rats longitudinally (imaging adolescents first at age 30 days and a second time at age 60 days, adults at age 60 days then again at age 90 days), to obtain a within-subject characterization of the long-term changes to D2R binding that occur in response to treatment. This experiment will provide us with in-vivo insight into how nicotine administration at different ages affects the dopaminergic system. By focusing on molecular consequences of nicotine exposure in adolescence, this work provides an opportunity to inform future prevention measures and potential medication treatments for addiction, as well as a greater understanding of adolescent brain development.